Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study

被引：139
作者：
Moon, Gyeong Joon [1 ,2 ]
Sung, Ji Hee [1 ,3 ]
Kim, Dong Hee [1 ,3 ]
Kim, Eun Hee [1 ,3 ]
Cho, Yeon Hee [1 ,3 ]
Son, Jeong Pyo [1 ,4 ]
Cha, Jae Min [5 ]
Bang, Oh Young [1 ,3 ,4 ,6 ]
机构：
[1] Sungkyunkwan Univ, Sch Med, Translat & Stem Cell Res Lab Stroke, Seoul 06351, South Korea
[2] Kyungpook Natl Univ, Sch Life Sci, BK21 Plus KNU Creat BioRes Grp, Daegu 41566, South Korea
[3] Samsung Med Ctr, Stem Cell & Regenerat Med Inst Future Med, Seoul 06351, South Korea
[4] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Seoul 06351, South Korea
[5] Incheon Natl Univ, 3D Stem Cell Bioproc Lab, Dept Mechatron, Incheon 22012, South Korea
[6] Sungkyunkwan Univ, Sch Med, Dept Neurol, Samsung Med Ctr, Seoul 06351, South Korea
来源：
TRANSLATIONAL STROKE RESEARCH | 2019年 / 10卷 / 05期
关键词：
Stroke; Mesenchymal stem cells; Extracellular vesicles; Neurogenesis; Angiogenesis; MicroRNAs; STROMAL CELLS; PROMOTE ANGIOGENESIS; IN-VITRO; MICROVESICLES; ISCHEMIA; HYPOXIA; METAANALYSIS; PLASTICITY; FORELIMB; DELIVERY;
D O I：
10.1007/s12975-018-0668-1
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Mesenchymal stem cells (MSCs) exert their therapeutic capability through a variety of bioactive substances, including trophic factors, microRNAs, and extracellular vesicles (EVs) in infarcted tissues. We therefore hypothesized that MSC-derived EVs (MSC-EVs) possess therapeutic molecules similar to MSCs. Moreover, given their nature as nanosized and lipid-shielded particles, the intravenous infusion of MSC-EVs would be advantageous over MSCs as a safer therapeutic approach. In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model. MSC-EVs successfully stimulated neurogenesis and angiogenesis in vivo. When compared to the MSC-treated group, rats treated with MSC-EVs exhibited greater behavioral improvements than the control group (p < 0.05). Our biodistribution study using fluorescence-labeled MSC-EVs and MSCs demonstrated that the amounts of MSC-EVs in the infarcted hemisphere increased in a dose-dependent manner, and were rarely found in the lung and liver. In addition, MSC-EVs were highly inclusive of various proteins and microRNAs (miRNAs) associated with neurogenesis and/or angiogenesis compared to fibro-EVs. We further analyzed those miRNAs and found that miRNA-184 and miRNA-210 were essential for promoting neurogenesis and angiogenesis of MSC-EVs, respectively. MSC-EVs represent an ideal alternative to MSCs for stroke treatment, with similar medicinal capacity but an improved safety profile that overcomes cell-associated limitations in stem cell therapy.
引用
收藏
页码：509 / 521
页数：13
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